Severe diseases or conditions such as primary hyperoxaluria (PH), secondary hyperoxaluria (SH), and Zellweger spectrum disorders (ZSD) continues to be a healthcare problem. These diseases occur when oxalate is readily absorbed from dietary sources or from liver overproduction. Oxalate absorption and secretion occur throughout the entire gastrointestinal (GI) tract, but net flow reflects absorption. High concentrations of oxalate and deposition of calcium oxalate (CaOx) crystals in the kidneys can evoke an inflammatory response and induce tubulointerstitial damage leading to fibrosis, loss of nephrons, and eventually to chronic and end-stage renal failure. CaOx supersaturation in blood can result in CaOx crystal deposition in multiple organs, which can cause organ dysfunction or transplanted organ failure. There is currently no effective treatment for such conditions. Therefore, the approach underlying this application is to reduce urinary and plasma oxalate by limiting dietary absorption and by increasing the oxalate secretion rate from the blood to the GI tract where soluble metabolically derived oxalate can be continuously removed by two highly active purified oxalate-degrading enzymes that are capable of removing oxalate throughout the vast GI tract. PUBLIC HEALTH RELEVANCE: Severe disease conditions, such as primary hyperoxaluria, secondary hyperoxaluria, and Zellweger sprectrum disorders, which are the result of increased dietary absorption or metabolic synthesis of oxalate continues to be a healthcare problem. Since there is currently no effective treatment at degrading oxalate throughout the entire GI tract, Captozyme is proposing to develop a combination of oxalate-degrading enzymes that can effectively intercept dietary oxalate as well as remove metabolically generated oxalate throughout the vast GI tract.